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M.ª TERESA MIRAS-PORTUGAL Y COLS. ANAL. REAL ACAD. NAC. FARM.

for ATP metabotropic calcium responses in single type 1 astrocytes.
All tested astrocytes responded to ATP and UTP stimulations evoking
similar calcium transients. Most astrocytes also responded to 2-
MeSADP and ADP challenges. The agonist potency and cross-
desensitization experiments demonstrated the presence of functional
P2Y1 and P2Y2 or P2Y4 receptors. In addition, the existence of an
astrocyte subpopulation that express functional P2Y6 was de-
monstrated, this accounting for 30-40% of the total.

In addition to phospholiphase C activation, PLC, and subsequent
calcium increase from internal stores, P2Y1,2,4,6 receptors, can also
activate the ERKs signalling cascade as they increase in western blot
the phosphorylated forms of ERK1 and ERK2 (79).

P2X functional responses in astrocytes

Recent data from our group support the presence of functional
ionotropic P2X7 nucleotide receptors in cerebellar astrocytes.
Although both P2X4 and P2X7 receptors were expressed at the protein
level, the responses found with the specific agonist BzATP are in
agreement with the activation of a P2X7 type, which exhibits a
distinctive behaviour in astrocytes. BzATP-induced calcium increases
are sustained, and not transient, as those obtained with the
metabotropic agonists 2MeSADP or UTP and far from inducing cell
lysis as described for P2X7 receptors from macrophages. Moreover,
stimulation of P2X7-like receptor induces significant morphological
changes in astrocytes and leads to differentiation (84).

CONCLUSIONS

Nucleotide receptors are very abundant at the central nervous
system, in all types of neural cells. Their physiological roles are far
from being elucidated and only fragmentary data are available.
However, there are increasing evidence concerning their involvement
in neuropathogenesis due to aging and neurotrauma. The specific
distribution and signalling cascades asociated with their neuronal
location, as soma, dendritic or axonal subcellular distribution, should

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